Abstract: The present invention provides compositions and methods for the treatment or prevention of a lysosomal disease or disorder involving increasing the level, expression, or activity of a metallothionein polypeptide or polynucleotide in the subject.

Abstract: The disclosure provides a composition for suppressing inflammation comprising at least one substance that disrupts a stem-loop structure in the 3? untranslated region of a Regnase-1 mRNA, wherein the stem-loop structure is at least one stem-loop structure selected from a first stem-loop structure formed in a region corresponding to positions 231 to 245 of SEQ ID NO: 1 and a second stem-loop structure formed in a region corresponding to positions 424 to 442 of SEQ ID NO: 1.

Abstract: This disclosure relates to RNA interference (RNAi) reagents for treatment of hepatitis B virus (HBV) infection, compositions comprising same, and use thereof to treat individuals infected with HBV. The reagents are artificial miRNA (shmiRNA) used alone or in combination with additional shmiRNA or shRNA.

Abstract: Provided herein, inter alia, are double stranded oligonucleotide molecules and methods of making the molecules. The double stranded oligonucleotide molecules include a first oligonucleotide strand comprising a first nucleic acid sequence bound to a second nucleic acid sequence through a first spacer, wherein said second nucleic acid sequence is bound to a third nucleic acid sequence through a second spacer and a second oligonucleotide strand comprising a fourth nucleic acid sequence bound to a fifth nucleic acid sequence through a third spacer, wherein said fifth nucleic acid sequence is bound to a sixth nucleic acid sequence through a fourth spacer, wherein the second nucleic acid sequence and the fifth nucleic acid sequence are hybridized to form a double stranded nucleic acid core of said double stranded oligonucleotide.

Abstract: Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.

Abstract: The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 400 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in direction selective retinal ganglion cells of a gene when operatively linked to a nucleic acid sequence coding for said gene.

Abstract: In an embodiment, the invention provides a method and reagents for detection of ?-herpesvirus circRNA. In another embodiment, the invention provides a method and reagents for detection of EBV circRNA. In still another embodiment, the invention provides a method and reagents for detection of KSHV circRNA. The method can be expanded to other herpesviruses and even non-herpesviruses that generate circRNA upon cellular infection.

Abstract: The disclosure is directed to inhibitory agents that hybridize to a GAPLINC RNA and inhibit or reduce the expression of the GAPLINC RNA. The GAPLINC RNA is a long non-coding RNA (lncRNA) located on chromosome 18 between the protein-coding genes Tgif and Dlgap1. The disclosure also features pharmaceutical compositions including the inhibitory agents and methods of using the inhibitory agents to treat an inflammatory disease, such as sepsis.

Abstract: The present disclosure relates to double stranded RNA agents targeting the hepatitis B virus (HBV) genome, and methods of using such agents to inhibit expression of one or more HBV genes and methods of treating subjects having an HBV infection or HBV-associated disorder, e.g., chronic hepatitis B infection.

Abstract: The present invention relates to a method for treating a Leber congenital amaurosis in a patient harbouring the mutation c.2991+1655 A>G in the CEP290 gene, comprising the step of administering to said patient at least one antisense oligonucleotide complementary to nucleic acid sequence that is necessary for preventing splicing of the cryptic exon inserted into the mutant c. 2991+1655 A>G CEP290 mRNA.

Abstract: Embodiments of the disclosure include methods and compositions for the renewal of cardiomyocytes by targeting the Hippo pathway. In particular embodiments, an individual with a need for cardiomyocyte renewal is provided an effective amount of a shRNA molecule that targets the Sav1 gene. Particular shRNA sequences are disclosed.

Abstract: Embodiments of the disclosure include methods and compositions for in situ cardiac cell regeneration, including transdifferentiation of cardiac cells to cardiomyocytes. In particular embodiments, in situ cardiac cell regeneration encompasses delivery of p63 shRNA and one or both of Hand2 and myocardin, and in specific embodiments further includes one or more of Gata4, Mef2c, and Tbx5. In specific aspects of the disclosure, adult cardiac fibroblasts are reprogrammed into cardiomyocytes using viral vectors that harbor p63 shRNA and one or both of the transcription factors Hand2 and myocardin.

Abstract: The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the angiotensinogen (AGT) gene, and methods of using such RNAi agents to inhibit expression of AGT and methods of treating subjects having an AGT-associated disorder, e.g., hypertension.

Abstract: A method of evaluating quality of miRNA derived from a body fluid sample includes a measuring step; comparing a measured value(s) of the abundance(s) of the one or more reference miRNAs in a body fluid sample or a representative value thereof to a measured value(s) of the abundance(s) of the one or more reference miRNAs in a standard body fluid sample or a representative value thereof, to obtain a difference(s) or a ratio(s) of the measured value(s) of the abundance(s) of the one or more reference miRNAs or the representative value thereof between the body fluid sample and the standard body fluid sample; and judging the quality of the miRNA derived from the body fluid sample based on the difference(s) or the ratio(s) of the measured value(s) of the abundance(s) of the one or more reference miRNAs or the representative value thereof obtained in the comparing step.

Abstract: This invention provides compounds, compositions and methods for modulating the expression of target genes using RNA interference. RNAi structures and molecules of this invention can be used for modulating or silencing the expression of genes, with high levels of RNAi activity and reduced off target actions. Advantageous structures include siRNAs targeted to any gene having one or more 2?-deoxy nucleotides located in the seed region. The RNA interference molecules can be used in methods for preventing or treating diseases.

Abstract: Disclosed herein are antisense compounds and methods for decreasing Factor 11 and treating or preventing thromboembolic complications in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 11 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Antisense compounds targeting Factor 11 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism.

Abstract: The subject invention provides a pharmaceutical composition comprising an inhibitory RNA (iRNA) that mediates sequence-specific degradation of the mRNA encoding Poly (ADP-ribose) polymerase 1 (PARP1) and methods of treating cancers by administering the pharmaceutical composition to a subject in need thereof. In one embodiment, the iRNA is miR-223, particularly, miR-223-3p or a modified miR-223-3p having substitutions and/or deletions in the sequence of miR-223-3p. In another embodiment, the cancer cells comprise one or more mutations in the genes that mediate homologous recombination DNA repair, for example, BRCA1 and/or BRCA2 genes. The cancer can be breast cancer, ovarian cancer, prostate cancer, pancreatic cancer or meso thelioma. Methods of treating cancer, for example, a cancer comprising BRCA1 and/or 2 mutations, using a combination of iRNA and a second cancer therapeutic are also provided.

Abstract: This invention provides compounds, compositions and methods for modulating the expression of target genes using RNA interference. RNAi structures and molecules of this invention can be used for modulating or silencing the expression of genes, with high levels of RNAi activity and reduced off target actions. Advantageous structures include siRNAs targeted to any gene having one or more 2?-deoxy nucleotides located in the seed region. The RNA interference molecules can be used in methods for preventing or treating diseases.

Abstract: Retrotransposons, operating though human-specific neurological pathways, can contribute to environment, lifestyle, and/or age-related neurodegeneration by disrupting functional mitochondrial populations within neurons. The mitochondrial disruption can occur through a number of retrotransposon-induced mechanisms that can influence the efficient and accurate transcription and/or translation of mitochondrial genes encoded in the nuclear genome, operating primarily through epigenetic processes. Alu element-related conformational changes (both subtle and major) of the outer and inner mitochondrial membrane pores can restrict or prevent the normal translocation of proteins (i.e., TOMM and TIMM complexes), ultimately contributing to mitochondrial stress, mitophagy, inflammation, and neuron and glial cell death.

Abstract: The present invention relates to stem cell-derived microvesicles with enhanced efficacy, a use thereof, and a method for enhancing efficacy, and more particularly, to a use of stem cell-derived microvesicles with an enhanced expression level of microRNAs for the prevention or treatment of stroke, and a method for promoting the production of microRNAs of stem cell-derived microvesicles and enhancing efficacy, and a method for promoting the production of stem cell-derived microvesicles and microRNAs within the microvesicles and enhancing the efficacy of stem cells and microvesicles thereof by 3-dimensionally culturing or ischemically stimulating stem cells.